Gabapentin

Gabapentin is described as 1-(aminomethyl) cyclohexaneacetic acid . C9H17NO2

Category:

Anticonvulsant, Antineuralgic(USP DI 2007)

Mechanism of action:

The mechanism of action is unknown . Gabapentin does not interact with GABA receptors, is not metabolized to GABA agonist or to GABA, and does not inhibit GABA uptake or degradation . In rats, gabapentin interacts with a novel binding site on cortical neurons that may be associated with the L-system amino acid transporter of brain cell membranes . Analgesic action – The mechanism of action is unknown. Gabapentin prevents pain – related behavior in response to a normally innocuous stimulus (allodynia) and exaggerated response to painful stimuli (hyperalgesia) in animal models. In models of neuropathic pain in rats or mice, gabapentin prevents pain-related responses. Pain-related responses after peripheral inflammation were also decreased by gabapentin . Immediate pain-related behaviors were not altered by gabapentin . (USP DI 2007)

Renal – Entire absorbed dose, as unchanged drug. Gabapentin clearance is directly proportional to creatinine clearance. Higher oral clearance values were observed in children < 5 years of age when normalized per body weight. In infants <1 year of age. Clearance was highly variable . In dialysis- Gabapentin can be removed from plasma by hemodialysis . (USP DI 2007)

Indications :

Accepted Epilepsy (treatment adjunct) – Gabapentin is indicated as an adjunct to other anticonvulsant medications (in the treatment of partial seizures with or without secondary generalization in adults and adolescents) with epilepsy . Gabapentin is also indicated as adjunctive therapy for the treatment of partial seizures in pediatric patients 3 years of age and older with epilepsy . Postherpetic Neuralgia – Gabapentin is indicated for the management of postherpetic neuralgia in adults . [Pain , peripheral neuropathic , diabetic (treatment)] – Gabapentin is indicated for the treatment of diabetic peripheral neuropathic pain .(USP DI 2007)

Contraindications :

Gabapentin is contraindicated in patients who have demonstrated hypersensitivity to the drug or its ingredients . (PDR 2008)

Warning :

Neuropsychiatric adverse Events- Pediatric patients 3-12 years of age : Gabapentin use in pediatric patients with epilepsy 3-12 years of age is associated with the occurrence of central nervous system related adverse events . The most significant of these can be classified into the following categories : 1) Emotional lability 2) Hostility 3) Thought disorder 4) Hyperkinesia Among the gabapentin – treated patients , most of the events were mild to moderate in intensity . Withdrawal precipitated seizure, status epilepticus : Antiepileptic drugs should not be abruptly discontinued because of the possibility of increasing seizure frequency .

Tumorigenic potential :

In standard preclinical invivo lifetime carcinogenicity studies, an unexpectedly high incidence of pancreatic acinar adenocarcinomas was identified in male, but not female, rats . Sudden and unexplained death in patients with epilepsy sudden death could represent seizure- related deaths in which the seizure was not observed, e.g.at night .(PDR 2008)

Precautions :

Patients should be instructed to take gabapentin only as prescribed . Patients should be advised that gabapentin may cause dizziness, somnolence and other symptoms and signs of CNS depression . Accordingly, they should be advised neither to drive a car nor to operate other complex machinery until they have gained sufficient experience on gabapentin to gauge whether or not it affects their mental and/or motor performance adversely . Patients who require concomitant treatment with morphine may experience increases in gabapentin concenteration . Patients should be carefully observed for signs of CNS depression, such as somnolence, and the dose of gabapentin or morphine should be reduced appropriately .(PDR 2008)

Missed dose :

Taking as soon as possible, if less than 2 hours until next dose, taking missed dose immediately and taking next dose 1 to 2 hours later then resuming regular dosing schedule, not doubling doses . (USP DI 2007)

Pregnancy:

FDA Pregnancy Category C : Gabapentin should be used be during pregnancy only if the benefit justifies the potential risk to the fetus. (USP DI 2007)

Breast – feeding :

Gabapentin is distributed into human breast milk following oral administration . A nursed infant could be exposed to a maximum dose of approximately 1 milligram per kilogram per day . Gabapentin should be used in women who are nursing only if the benefits clearly outweight the risks .(USP DI 2007)

Geriatrics :

Plasma clearance of gabapentin is reduced in the elderly , probably due to age-related renal function decline . Dosage reduction based on creatinine clearance is recommended . Further dosage adjustments should be based on clinical response .(USP DI 2007)

Usual adult and adolescent dose : -Anticonvulsant : Oral, initially 300 mg three times a day . The dosage may be gradually increased based on clinical response . Dosages of 900 to 1800 mg per day are effective for most patients .However, dosages as high as 2400 to 3600 mg/day have been well tolerated . Note : Dosage may be increased more slowly to avoid CNS adverse effects . When taking gabapentin three times a day , the maximum time between doses should not exceed twelve hours . For patients with renal function impairment : See Usual geriatric dose . Postherpetic neuralgia: Usual adult dose : Oral , initial single dose of 300 milligram on day 1 : 600 milligrams per day (divided, two times a day) on day 2 ; 900 milligrams per day (divided , three times a day ) on day 3 . Dose may be titrated up to a maximum daily dose of 1800 milligrams (divided, three times a day) . additional benefits were not demonstrated at doses greater than 1800 milligrams per day . Note : For patients with renal function impairment: See Usual geriatric dose. - Diabetic peripheral neuropathic pain: Usual adult dose : Oral, initially 900 mg/day titrated to maximum of 3600 mg/ day . Note : Adults with renal function impairment ma require a reduction in dose as follows - Creatinine clearance (CrCl) > 60: Up to 1800 mg a day . - CrCl = 30 – 60 ml per minute : 300 mg two times a day . - CrCl = 15 – 30 ml per minute : 300 mg per day . - CrCl < 15 ml per minute : 300 mg every other day .

Usual adult and adolescent prescribing limits :

3600 mg/day -Usual pediatric dose : -Anticonvulsant : Children 3 to 12 years : The starting dose should rang from 10 to 15 mg/kg per day, divided into three doses . The effective dose should be reached by upward titration over a period of approximately 3 days. Ages 5 years and older : The effective dose is 25 to 35 mg / kg per day given in divided doses . Ages 3 years and 4 years : The effective dose is 40 mg/kg per day given in divided doses .

Usual pediatric prescribing limit:

Dosage of up to 50 mg/kg per day have been well tolerate in long term clinical studies .

Usual geriatric dose:

Oral, initial dosage recommendations, based on creatinine clearance . Dosage adjustment may be made based on clinical response . The Dosage can be 300 mg one every other day to 3600 mg/day in renal impairment (USP DI 2007)